Irish women are set to benefit from a quiet revolution in breast cancer treatment. Kathrine Burke reports
For some breast cancer patients, cancer returns after treatment, while others live to old age without further symptoms. Primary treatment usually involves radiotherapy and surgery and is normally followed by chemotherapy and additional treatments to ensure that cancer does not come back.
Like fingerprints or any other biometric, tumours are genetically unique to the individual and behave differently.
This is the basis for new pan-European research that aims to use genetic information to individually tailor breast cancer treatment in the future and to distinguish who needs chemotherapy and who does not.
In Brussels this summer, the project co-ordinator, Dr Martine Piccart, said the anticipated benefit of "refined prognosis will allow for better definition of who needs treatment and can thereby reduce the proportion of women receiving unnecessary chemotherapy. This would reduce their exposure to toxicity and harmful long-term side-effects, while significantly reducing the burden of breast cancer therapy and its burden on healthcare systems."
Dr Maccon Keane, consultant oncologist at University College Hospital, Galway, says genetic profiling is the most recent milestone in breast cancer treatment.
Past milestones include work in the late 1960s which found that radical mastectomy was not required for all women with breast cancer, and the advent of chemotherapy and hormone treatments over the 1970s and 1980s.
The consultant leading Ireland's participation in this research is Dr Arnold Hill from St Vincent's University Hospital. The hospital will act as the main centre in Ireland, co-ordinating recruitment of Irish patients to the study.
While Dr Hill agrees that knowledge of the genetic aspect of cancer is "leaping forward", he strongly emphasises that media reports on the research should be sensitive to the hopes and fears of women with breast cancer.
PROGNOSIS
The method of prognosis used today to decide a treatment schedule looks at factors such as size of the tumour, whether cancer has spread to the lymph nodes, and whether the woman is likely to respond to hormonal treatments. But, according to the network co-ordinating this research, this is an inexact procedure, and chemotherapy over-treatment is estimated at 12 to 20 per cent.
The proposed new method of prognosis will instead analyse the genetic profile of a woman's tumour.
Genetic profiling of breast cancers was pressed forward by a paper by Van de Leer et al, a Dutch team of scientists, published in the New England Journal of Medicine in 2001.
The group identified a sequence of 70 genes, which seemed to predict breast cancer survival rates.
They then looked retrospectively at tissue samples from women who were diagnosed with breast cancer in the 1960s. Given the era, these women had not been treated with chemotherapy.
When they compared the 70-gene "signature" in these tissue samples with patient records, the researchers found that the signature indeed predicted the patients' prognosis: It foretold which women would have recurrence of the cancer on the one hand, and which women survived without further disease.
None of these women had received chemotherapy, yet a proportion of the group survived.
The major significance is that the 70-gene signature should enable doctors today to determine which women need chemotherapy and which women do not.
PROJECT
The MINDACT (Microarray for Node Negative Disease may Avoid ChemoTherapy) project, which is the first such scheme approved for Commission funding, was designed to exploit these findings.
The next step is to repeat and confirm the result using tissue samples from 1960s patients at Oxford in the UK, beginning this year.
When this is complete, anticipated by 2008, St Vincent's Hospital will begin to apply the results.
Dr Hill's group will analyse the 70-gene signatures of current breast cancer patients and avoid chemotherapy where the genetic profile indicates low risk of recurrence.
MINDACT specifically concerns genetic profiling of women whose cancer has not yet spread to the lymph nodes.
"That is an increasing group of patients as cancer is identified early by screening programmes," says Dr Maccon Keane.
"Currently, we cannot identify upfront which women are likely to benefit from chemotherapy," he says.
He agrees that this probably means that one group of patients is being over-treated, but adds that they may be under-treating a group of patients who they think will do well based on traditional prognosis, but who have poor genetic prognosis.
It is not possible to find out from the Department of Health how much the health service spends on chemotherapy each year. Its press office explained that the Department does not collate those figures and suggested calling the various health boards and hospitals individually.
Where cancer has spread to the lymph nodes, chemotherapy is estimated to cost about €1,500 per cycle for about eight cycles.
The biotechnology and bioinformatics technologies behind molecular profiling are already well developed, but are expensive, and no standard laboratories can provide the service to healthcare yet in Ireland.
Dr Keane chairs the group on genetics on the National Cancer Forum. He envisages that molecular profiling will become the standard of care in designing treatments for patients within the next few years.
"Molecular profiling needs properly validated labs that are properly resourced. We would expect that this will be done in the four proposed supra-national regional labs," he says.
"It is certainly one of the costs that will be flagged to the Government in the next cancer strategy document."
Research should be part of standard care, according to Dr Keane. With more research being conducted in Ireland, Irish women with breast cancer are getting more exposure to that research, he says.
He gives an example of where this has already benefited patients. "We were a high recruiter for clinical trials of a targeted molecular treatment called Receptin over the last few years. That meant that Irish women got that drug much earlier on a research protocol. It hasn't yet become standard of care, but women here are treated in that way."
He argues that research protocols should be offered to all patients. "There is an awful lot that we don't know about these diseases. Every patient should be offered some research protocol to have further knowledge of the disease.
"I think that the more patients who are enrolled in clinical trials and research projects, the better the outcomes will be for everybody."
Keane is a member of the Marie Keating Foundation, which raises funds to provide information about breast cancer to anyone who wants it. Its slogan is: "To enlighten not to frighten."